A patient-specific therapeutic approach for tumour cell population extinction and drug toxicity reduction using control systems-based dose-profile design

Purpose We developed a compact and lightweight time-resolved mirrorless scintillation detector (TRMLSD) employing image processing techniques and a convolutional neural network (CNN) for high-resolution two-dimensional (2D) dosimetry. Methods The TRMLSD comprises a camera and an inorganic scintillator plate without a mirror. The camera was installed at a certain angle from the horizontal plane to collect scintillation from the scintillator plate. The geometric distortion due to the absence of a mirror and camera lens was corrected using a projective transform. Variations in brightness due to the distance between the image sensor and each point on the scintillator plate and the inhomogeneity of the material constituting the scintillator were corrected using a 20.0 × 20.0 cm2 radiation field. Hot pixels were removed using a frame-based noise-reduction technique. Finally, a CNN-based 2D dose distribution deconvolution model was applied to compensate for the dose error in the penumbra region and a lack of backscatter. The linearity, reproducibility, dose rate dependency, and dose profile were tested for a 6 MV X-ray beam to verify dosimeter characteristics. Gamma analysis was performed for two simple and 10 clinical intensity-modulated radiation therapy (IMRT) plans. Results The dose linearity with brightness ranging from 0.0 cGy to 200.0 cGy was 0.9998 (R-squared value), and the root-mean-square error value was 1.010. For five consecutive measurements, the reproducibility was within 3% error, and the dose rate dependency was within 1%. The depth dose distribution and lateral dose profile coincided with the ionization chamber data with a 1% mean error. In 2D dosimetry for IMRT plans, the mean gamma passing rates with a 3%/3 mm gamma criterion for the two simple and ten clinical IMRT plans were 96.77% and 95.75%, respectively. Conclusion The verified accuracy and time-resolved characteristics of the dosimeter may be useful for the quality assurance of machines and patient-specific quality assurance for clinical step-and-shoot IMRT plans.

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The 1980s: A patient-specific therapeutic approach in hypertension

American Heart Journal ◽

10.1016/0002-8703(87)90967-7 ◽

1987 ◽

Vol 114 (1) ◽

pp. 224-226 ◽

Cited By ~ 2

Author(s):

Vincent DeQuattro

Keyword(s):

Therapeutic Approach ◽

Patient Specific

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OncoVEX: A family of oncolytic herpes simplex viruses optimised for therapeutic use

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.13139 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 13139-13139

Author(s):

R. S. Coffin ◽

B. Liu ◽

Z. Han ◽

M. Assenberg ◽

S. Thomas ◽

...

Keyword(s):

Phase I ◽

Tumour Cell ◽

Patient Specific ◽

Phase I Clinical Trials ◽

Herpes Simplex Viruses ◽

Tumour Control ◽

Gm Csf ◽

Local Tumour Control ◽

Phase Ii Studies

13139 HSV in which ICP34.5 is deleted directs tumour selective cell lysis and has proven safe in Phase I clinical trials. To produce oncolytic HSV with enhanced anti-tumour properties, we have deleted ICP34.5 from a clinical isolate of HSV-1, which enhances the tumour cell killing capabilities of the virus, deleted ICP47 (which blocks antigen presentation), and inserted the gene encoding GM-CSF. This aimed to maximize anti-tumour immune responses following intra-tumoural injection and provide an in situ, patient-specific, anti-tumour vaccine, combined with oncolysis. In vivo, both injected and non-injected tumours could be cured and animals were then protected against tumour cell challenge. A Phase I clinical trial with the virus (OncoVEXGM-CSF) has been conducted including patients with cutaneous or sub-cutaneous deposits of a number of tumour types (Lead Investigator: Professor Charles Coombes, Hammersmith Hospital, London). This demonstrated the virus to have a good safety profile, the main side effects being ‘flu-like symptoms, similar to those which have previously been observed with other oncolytic products. Virus replication and GM-CSF expression was demonstrated together with inflammation, flattening and necrosis of injected lesions which was in some cases considerable and which was also in some cases observed in lesions which had not themselves been injected. In all cases where necrosis was observed in biopsies, this correlated with areas of staining for HSV, suggesting the virus had caused the effect. Following this promising data, Phase II studies are underway in multiple tumour types. In addition to OncoVEXGM-CSF, further versions of OncoVEX expressing other active genes have been constructed and tested in pre-clinical models. These include a virus expressing TNF∝, intended to be synergistic with radiotherapy, and versions of the virus expressing a pro-drug activating gene combined with the delivery of a fusogenic glycoprotein designed to maximize the properties of the virus for local tumour control. Each of these have shown promising results in pre-clinical tumour models, including in combination with chemotherapy and radiotherapy where benefits which are at least additive have been demonstrated. [Table: see text]

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Corrective Osteotomy of Upper Extremity Malunions Using Three-Dimensional Planning and Patient-Specific Surgical Guides: Recent Advances and Perspectives

Frontiers in Surgery ◽

10.3389/fsurg.2021.615026 ◽

2021 ◽

Vol 8 ◽

Author(s):

Babak Saravi ◽

Gernot Lang ◽

Rebecca Steger ◽

Andreas Vollmer ◽

Jörn Zwingmann

Keyword(s):

Range Of Motion ◽

Upper Extremity ◽

Therapeutic Approach ◽

Corrective Osteotomy ◽

Three Dimensional ◽

Current Evidence ◽

Patient Specific ◽

Computer Assisted ◽

Surgical Guides ◽

Recent Advances

Malunions of the upper extremity can result in severe functional problems and increase the risk of osteoarthritis. The surgical reconstruction of complex malunions can be technically challenging. Recent advances in computer-assisted orthopedic surgery provide an innovative solution for complex three-dimensional (3-D) reconstructions. This study aims to evaluate the clinical applicability of 3-D computer-assisted planning and surgery for upper extremity malunions. Hence, we provide a summary of evidence on this topic and highlight recent advances in this field. Further, we provide a practical implementation of this therapeutic approach based on three cases of malunited forearm fractures treated with corrective osteotomy using preoperative three-dimensional simulation and patient-specific surgical guides. All three cases, one female (56 years old) and two males (18 and 26 years old), had painful restrictions in range of motion (ROM) due to forearm malunions and took part in clinical and radiologic assessments. Postoperative evaluation of patient outcomes showed a substantial increase in range of motion, reduction of preoperatively reported pain, and an overall improvement of patients' satisfaction. The therapeutic approach used in these cases resulted in an excellent anatomical and functional reconstruction and was assessed as precise, safe, and reliable. Based on current evidence and our results, the 3-D preoperative planning technique could be the new gold standard in the treatment of complex upper extremity malunions in the future.

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